Inhibition Of Iron Ions On The Quorum Sensing System Of Pseudomonas Aeruginosa And Its Mechanism

Pseudomonas aeruginosa(PA),an opportunistic pathogen widely presented in the environment,can cause a variety of disease infections,such as skin burns,lung infections,and cystic fibrosis.About 80 % of adult patients with cystic fibrosis(CF)die of pulmonary function and eventually respiratory failure due to Pseudomonas aeruginosa infection,mainly because Pseudomonas aeruginosa can regulate the production of multiple virulence factors through the quorum sensing(QS)system.In addition,PA is able to enhance its ability to adapt to the pulmonary environment of CF patients through genotypic or phenotypic alterations.It has been reported in the literature that a large number of wild-type and las R mutant strains of Pseudomonas aeruginosa can be isolated from the lungs of CF patients with long-term chronic infections,and very abundant aggregates of iron ions and transferrin have been found in the lungs of CF patients,but the association between iron ions and Pseudomonas aeruginosa infection and las R mutant strains is unclear.In order to solve this problem,the las R gene of Pseudomonas aeruginosa was knocked out in this study.The wild type and Δlas R strains of Pseudomonas aeruginosa were then cultured under iron-rich and iron-deficient conditions and analyzed by proteomics technology.It was found that iron ions can significantly inhibit the expression of Pseudomonas aeruginosa quorum sensing system.Inhibiting the production of siderophore and pyocyanin;Through the experiments of gene overexpression and quorum sensing signal molecules,we found that the iron ions further inhibited the quorum sensing system of Pseudomonas aeruginosa by inhibiting pvd Q,and it may be closely related to the biosynthesis of siderophore.In addition,we found that iron ions can inhibit the formation of bacterial biofilms and swarming motility by inhibiting Pseudomonas aeruginosa’s quorum-sensing system.Finally,to simulate the population ratio of Pseudomonas aeruginosa in the lungs of CF patients enriched with iron ions,in vitro competition experiments and whole genome resequencing techniques revealed that the proportion of quorum sensing mutants Δlas R of Pseudomonas aeruginosa was down-regulated in the iron-rich environment.In summary,this study provides a preliminary description of the molecular mechanisms by which the iron ions affects the growth and metabolism of Pseudomonas aeruginosa,and reveals that inhibition of the biosynthetic pathway of siderophore may become the target of an inhibitor drug of the quorum sensing system of Pseudomonas aeruginosa,providing a new perspective for the treatment of Pseudomonas aeruginosa infections.